Non‐invasive pulsed cavitational ultrasound for fetal tissue ablation: feasibility study in a fetal sheep model

Kim, Yejoong; Gelehrter, Sarah; Fifer, Carlen G.; Lu, Jimmy C.; Owens, Gabe E.; Berman, Deborah R.; Williams, J. F.; Wilkinson, John E.; Ives, Kimberly; Xu, Zhen

doi:10.1002/uog.8880

Cited by 39 publications

(36 citation statements)

References 23 publications

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“…Histopathologically, the thermal-treated mice revealed more confluent coagulation necrosis, while both M-HIFU-and inT-HIFU-treated groups showed more fractionated tissue necrosis and hemorrhage. These effects are similar as found in earlier studies on sheep, rats, or rabbits [8,35,36]. The mechanical effects were limited compared to thermal effects, still some dying cells and living cells were found between the fractionated tissues 3 days after the ablation.…”

Section: Discussionsupporting

confidence: 86%

Development of a high-field MR-guided HIFU setup for thermal and mechanical ablation methods in small animals

et al. 2015

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BackgroundThermal and mechanical high intensity focused ultrasound (HIFU) ablation techniques are in development for non-invasive treatment of cancer. However, knowledge of in vivo histopathologic and immunologic reactions after HIFU ablation is still limited. This study aims to create a setup for evaluation of different HIFU ablation methods in mouse tumors using high-field magnetic resonance (MR) guidance. An optimized MR-guided-HIFU setup could be used to increase knowledge of the different pathologic and immunologic reactions to different HIFU ablation methods.MethodsThree different HIFU treatment strategies were applied in mouse melanomas (B16): a thermal (continuous wave), a mechanical (5 ms pulsed wave), and an intermediate setting (20 ms pulsed wave) for HIFU ablation, all under MR guidance using a 7 tesla animal MR system. Histopathologic evaluation was performed 3 days after treatment.ResultsThe focus of the ultrasound transducer could accurately be positioned within the tumor under MR image guidance, without substantial damage to the surrounding tissue and skin. All mice retained complete use of the treated leg after treatment. Temperatures of >60, <50, and <44 °C were reached during thermal, intermediate, and mechanical HIFU ablation, respectively. Thermal-treated tumors showed large regions of coagulative necrosis. Tumors of both the mechanical and intermediate groups showed fractionated tissue with islands of necrosis and some pseudocysts with hemorrhage.ConclusionA stable small animal MR-guided HIFU setup was designed and evaluated for follow-up MR imaging and histopathologic responses of the treated tumors. This will facilitate further studies with a larger number of mice for detailed evaluation of the pathologic and immunologic response to different HIFU strategies.

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Section: Discussionsupporting

confidence: 86%

Development of a high-field MR-guided HIFU setup for thermal and mechanical ablation methods in small animals

et al. 2015

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“…More recently, investigators have safely harnessed cavitation to perform extracranial “histotripsy,” or the fractionation of tissue, for pathology involving cardiac, 1,28,32,38,39 prostate, 13,19 and fetal tissue. 18 …”

Section: Discussionmentioning

confidence: 99%

“…29 It has also been shown that focused ultrasound can be used to disintegrate tissue such that holes or tunnels are created. 13,18,19,32,38,39 To rapidly perforate or fractionate tissue, however, inertial cavitation is required as thermal mechanisms leave the tissue—at least acutely—structurally intact. Acoustic cavitation refers generally to the interaction of sound waves with gas bodies in a liquid medium.…”

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confidence: 99%

Cavitation-based third ventriculostomy using MRI-guided focused ultrasound

Alkins

Huang

Pajek

et al. 2013

JNS

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Object Transcranial focused ultrasound is increasingly being investigated as a minimally invasive treatment for a range of intracranial pathologies. At higher peak rarefaction pressures than those used for thermal ablation, focused ultrasound can initiate inertial cavitation and create holes in the brain by fractionation of the tissue elements. The authors investigated the technical feasibility of using MRI-guided focused ultrasound to perform a third ventriculostomy as a possible noninvasive alternative to endoscopic third ventriculostomy for hydrocephalus. Methods A craniectomy was performed in male pigs weighing 13–19 kg to expose the supratentorial brain, leaving the dura mater intact. Seven pigs were treated through the craniectomy, while 2 pigs were treated through ex vivo human skulls placed in the beam path. Registration and targeting was done using T2-weighted MRI sequences. For transcranial treatments a CT scan was used to correct the beam from aberrations due to the skull and maintain a small, high-intensity focus. Sonications were performed at both 650 kHz and 230 kHz at a range of intensities, and the in situ pressures were estimated both from simulations and experimental data to establish a threshold for tissue fractionation in the brain. Results In craniectomized animals at 650 kHz, a peak pressure ≥ 22.7 MPa for 1 second was needed to reliably create a ventriculostomy. Transcranially at this frequency the ExAblate 4000 was unable to generate the required intensity to fractionate tissue, although cavitation was initiated. At 230 kHz, ventriculostomy was successful through the skull with a peak pressure of 8.8 MPa. Conclusions This is the first study to suggest that it is possible to perform a completely noninvasive third ventriculostomy using ultrasound. This may pave the way for future studies and eventually provide an alternative means for the creation of CSF communications in the brain, including perforation of the septum pellucidum or intraventricular membranes.

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“…Reduction in vascularity may also reduce risks associated with haemorrhage at time of delivery. Animal studies have demonstrated that HIFU lesions in the fetal pelvis can be made despite the restrictions of the bony pelvis on the acoustic window [123], and that survival is compatible with the generation of necrotic tissue within the fetus [43,44]. HIFU represents a potential noninvasive therapy for SCT in the antenatal period, especially of fetuses with significant compromise in utero.…”

Section: Sacrococcygeal Teratomamentioning

confidence: 99%

“…This is of particular significance where the targets are small, or hard to locate, and the margin of error is limited. Injuries to bowel [15,44], nerves [20] or adjacent vessels [14] have been reported in fetal and vascular HIFU experiments, with or without associated vascular occlusion. Mistargeting is also an issue as not only does it fail to occlude the target vessels, but also repeat exposure is likely to be precluded until such time as tissue healing has been allowed to occur.…”

Section: Undesirable Effects Of High-intensity Focused Ultrasound Appmentioning

confidence: 99%

Pathophysiological mechanisms of high-intensity focused ultrasound-mediated vascular occlusion and relevance to non-invasive fetal surgery

Shaw

Haar

Rivens

et al. 2014

J. R. Soc. Interface.

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ReviewCite this article: Shaw CJ, ter Haar GR, Rivens IH, Giussani DA, Lees CC. 2014 Pathophysiological mechanisms of high-intensity focused ultrasound-mediated vascular occlusion and relevance to non-invasive fetal surgery. J. R. Soc. High-intensity focused ultrasound (HIFU) is a non-invasive technology, which can be used occlude blood vessels in the body. Both the theory underlying and practical process of blood vessel occlusion are still under development and relatively sparse in vivo experimental and therapeutic data exist. HIFU would however provide an alternative to surgery, particularly in circumstances where serious complications inherent to surgery outweigh the potential benefits. Accordingly, the HIFU technique would be of particular utility for fetal and placental interventions, where open or endoscopic surgery is fraught with difficulty and likelihood of complications including premature delivery. This assumes that HIFU could be shown to safely and effectively occlude blood vessels in utero. To understand these mechanisms more fully, we present a review of relevant cross-specialty literature on the topic of vascular HIFU and suggest an integrative mechanism taking into account clinical, physical and engineering considerations through which HIFU may produce vascular occlusion. This model may aid in the design of HIFU protocols to further develop this area, and might be adapted to provide a non-invasive therapy for conditions in fetal medicine where vascular occlusion is beneficial.

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Non‐invasive pulsed cavitational ultrasound for fetal tissue ablation: feasibility study in a fetal sheep model

Abstract: Objectives Currently available fetal intervention techniques rely on invasive procedures that carry inherent risks. A non-invasive

Cited by 39 publications

References 23 publications

Development of a high-field MR-guided HIFU setup for thermal and mechanical ablation methods in small animals

Development of a high-field MR-guided HIFU setup for thermal and mechanical ablation methods in small animals

Cavitation-based third ventriculostomy using MRI-guided focused ultrasound

Pathophysiological mechanisms of high-intensity focused ultrasound-mediated vascular occlusion and relevance to non-invasive fetal surgery

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